Document dkpOd1rgEVDVk536Z8jqEmxB

interimReport#1 Epidemiology2,20-3W-05 MedicalDepartment 3M Company St.Paul,NIN 55144 Date: June8,2000 TitleD:eterminationofSerum Half-Livesof SeveralFluorochemicals Study StartDate: EstimatedDate of FinalReport: IRB Approval Date: ProtocolNumber # 0007 IRB Approval # 98095 Exempt XX Expedited June,2004 14 October 1998 PrincipalInvestigator: Co-investigators: Jean M. Burris,RN, MPH' Geary Olsen,DVM, PhD' Cathy Simpson, RN2 JeffreyMandel, MD, MPH' Study Director: Study Sponsor: JeffreyMandel. NID, MPH' CorporateOccupationalMedicine Department 3M Company 220-3W-05 SaintPaul,MN 55144 1 OccupationalMedicine,Medical Department,3M Company, 220-3W-05, St. Paul,MN 55114 2. 3M DecaturSpecialtyAdhesives and Chemicals Plant,P.O. Box 2206, Decatur, AL 35609-2206 Page I ABSTRACT Previous estimatesregardingthe human serum half-lifoef perfluorooctanesulfonat(ePFOS) and perfluorooctanoate(PFOA) ranged between 10001500 days and 365-530 days respectively[Olsen etal.,1999, Ube] et al.,1980]. These estimateswere based on very few subjects.We arecurrentlyin theprocess of collecting datafrom 27 retiredf.luorochemicalproductionemployees inan effortto more completely estimatethe half-lifoef PFOS and PFOA along with fiveother fluorochemicalanalytes.To date,preliminaryanalysesfrom threeserum collection periodsutilizinag one compartment model suggeststhatthe serum half-lifoef PFOS in theseretireesislikelyto be four-foldlower than the range of 1000-1500 days thatwas previouslysuggested.The serum half-lifoef PFOA in theseretireesappears to be approximately one year,which iscomparable to theestimatesugcested by Ubel etal 1980]. Because of the lower limitof quantitatioanssayed forthe otherfluorochemical analytes,we believeadditionalcollectionperiodsare necessarybefore serum half-life calculationcsan be determined. There are severallimitationtso the currentreport,the most important bein- the paucityof data availableto date and the range of the serum levelsmeasured (PFOS range 0.2-2.Oppm, PFOA 0.1-3.1ppm). We anticipate completingtwo additionalserum collectioncyclesbeforeDecember 2000. Additional datashould allow a betterassessment of fluorochemicalhalf-liveosf allparticipantisn thisstudy. Page2 INTRODUCTION Althouc,hithas been reportedthattheserum half-lifoef perfluorooctanesulfoante (PFOS 1)and perfluorooctanoate(PFOA) in humans may range between 1000-1500 days and 365-530 days respectively[Olsen et al.,1999; Ubel etal.,19801,such estimations have been based on very few subjects. The purpose of thisstudy isto determine the serum half-lifferom a croup of Decatur and Cottage Grove retireesforthe following fluorochemicals:PFOS, PFOA, perfluorohexanesulfonat(ePFHS), N-ethyl perfluorooctanesulfonamidoaceta(tPeFOSAA), N-methyl perfluorooctanesulfonamdoaceta(tMe570), perfluorooctanesulfonamid(ePFOSA). and perfluorooctanesulfonamidoaceta(tMe556). METHODS Twenty-four Decatur retireeasnd threeCottage Grove retireeshave voluntarily participateidn multipleserum sample collectioncyclesforfluorochemicalanalysis.The majorityof the twenty-sevenparticipantasre male, only two arefemale. All participants are Iona-terrn3M employees. They have worked an average of 28 yearsin eitherthe Decatur or Cottage Grove chemical division.The average age of the participantatthe time of thefirsctollectioins60 years(range:55-74). The mean number of months from retirementto the startof the studyis30 months (range:5-130 months). To date,therehave been threeDecatur collectionperiods:November 1998, June 1999 and November 1999. Cottage Grove retireeshave participateidn two collection periods:June 1999 and November/December 1999. The next serum sampling is scheduled forMay 2000. Participanthsave receivedletterisnforming them of their Page 3 individualfluorochemicalresultsas data have become availablefrom the laboratory. Each participanctompletes a briefmedical historyquestionnairecontaininci,nformation about currentmedications,and diseasediagnosis.Responses have been keyed intoa SAS datasetand analyzed by JMP software. High -performance liquidchromatography mass spectrometry/massspectrometry has been utilizedto analyze allserum samples (NWB,1999). All samples were analyzed by Northwest BioanalyticaLlaboratory,SaltLake City,Utah with theexceptionof the M556 and M570 from November 1998. The 3M Environmental Technology and ServicesLaboratory analyzed these samples. Half-liveswere calculatedassuming a one compartment model. A log-linear relationshiwpas used toestimatethe serum fluorochemicaleliminationhalf-lifien participatinrgetirees.In thislog linearrelationshipt,he slopeof the lineisrelatedto the eliminationconstant(-k,lv)iatheequation: Slope = -k,1(2.303)O.nce theelimination constantiscalculated,the half-lifiesdeten-ninedusin-the relationshipt:,,=.,0.693/kel (Medinsky & Klassen,1996). RESULTS A totalof 24 participantpsrovided serum samples foreach collectionperiod.A half-lifweas calculatedforeach of theseindividualsforPFOS and PFOA. Except for PFHS, half-livefsorthe otherfluorochemicalswere not calculatedas the majoritywas below the limitof quantitatiobny the thirdcollection.Because the assay measurement of PFHS was inconsistent(e.g.m,any subsequentlycollectedsamples were athigher levels Page 4 than initiaslamples),thecalculatioonf thePFHS half-lifweas deferreduntilfurther blood collectionosccur. Table I presentsthe mean, median, range and 95% confidence intervalof the half-livecsalculatedforthoseretiree(sn=18 forPFOS, n=20 forPFOA) who were judged to have a good 2 fit(r > 0.6)fora linearone compartmental model for PFOS and PFOA. At thistime we have not includedthe otherparticipantisn theseanalysesfortwo reasons:1) lackof threedatapointsforsome subjects;and 2) lackof fitof model (i.e., r2,0 .6).The lattewras oftendue tothe factthatthe second measurement was higherthan the first.At thistime we are uncertainwhether thismay be due to subsequent exposure, biologicalvariationor assay errorand/orvariation.[Note:We are scheduled to collect two more datapointsby December 2000. By thattime we anticipateincludinz:cla,ll participantisn the analysis.] The ranee of serum PFOS measured was 0.2 -2.0 ppm (Table 1). The range of serum PFOA measured was 0.1 - 3.1 ppm. All PFOS serum half-lifcealculationwsere of male retireesT.wo of the 20 PFOA serum half-lifcealculationswere of female retirees. As can be seen from Table 1,the median serum half lifeof PFOS was 270 days 2 (range 139-640) forthe 18 male retireeswhose loLc-,linearreC-7 ressionmodel had an r -> 0.6.The median serum halflifeof PFOA was 344 days forthe 20 maie and female retireewshose loc,linearregressionmodel had an 2 r > 0.6. Restrictinct,he models to r2 > 0.8didnot substantiallcyhance thehalf-lifcealculationfsorPFOS or PFOA. Itshould be noted thatthe highestPFOA half-lifcealculationwsere from the two female retirees: 654 and 1308 days. Neitherage nor the number of months retiredwas associatedwith the serum half-lifcealculationfsor PFOS or PFOA. Page5 DISCUSSION The resultfsrom thisfirsitnterimanalysisuggestthattheserum half-lioffe PFOS inhumans islikelytobe four-foldlowerthan therange of 1000-1500 davs that was initiallsyugcested[Olsenetal.,1999].The serum half-lifoef PFOA inhumans appearsto be approximatelyone year,which iscomparable to theestimatesuggestedby Ubel etal[1980].Additionalcollectiocnycleswillfurtherefinethesehalf-lifeestimates and takeintoaccounttheretireewsho were excluded inthisinterimreportdue tolackof fitoftheone compartment model. This,ofcourse,assumes a one-compartment model is appropriateatthelow ppm serum levelsmeasured in thisgroup of retirees. Our resultsfrom thispreliminaryinterimanalysisshould be interpretecdautiously due tothepaucityof dataavailabletodate.The fourthdatapointisscheduledtobe collectedand analyzedby mid-summer. There areseveraladditionalimitationtsothese interimdata.To date,CottageGrove retireehsave participateidnonly two serum collectiocnvcies.Three of thetwenty-fourDecaturretireehsave indicatedateach serum collectiocnyclethattheyhave worked ina consultincc,apacityinthe3M Decaturplantat some pointduringtheinterveningsixmonths. However, theirloc,linearregression models were consideredtobe ofreasonablycood fit(i.e.r,2 forPFOS >-.80,i-f2orPFOA > .57).Four ofthesevenfluorochemicalanalvtes(PFOSAA, PFOSA. M556 and M570) measured below thelower limitofquantitatiofnormore than80% ofthesamples prohibitinag reasonablehalf-lifcealculationA.t thistime we areuncertainwhy many subsequentPFHS serum levelswere hicherthanthefirstmeasurement. With additional datawe hope todefinehalf-liveisnthesecompounds althoughiflevelsremain below the LLOQ thismay notbe feasible. Page 6 The next collectiopneriodwilloccur in May 2000 with anticipatedresultsdue back from Northwest Bloanalyticably mid-summer. Additionaldata should allow a betterassessmentof the half-liveosf allretireesT.he next interimreportshould be availableby August 2000. Page 7 REFERENCES Olsen GW, BurTisJM, Mandel JH, Zobel LR. Serum perfluorooctanesulfonateand hepaticand lipidclinicalchemistrytestsin fluorochemicalproductionemployees. J Occup Env Med 41:1999:799-806. Ubel F, Sorenson S, Roach D. Health statusof plantworkers exposed to fluorochemicals:a preliminaryreport.Am Ind HycZ,7, Assoc J 1980;41:584-589. NWB. QuantitativeDeterminationof PFOS, PFOSA, PFOSAA, POAA, and PFHS in Human Serum by LC/MS/MS. 1999. SaltLake City,Northwest Bioanalytica(lNWB) A Divisionof NWT Inc. Medinsky MA, Klaasen CD. Toxicokinetics(In)KlaasenCD (ed)Casarett& Doull's Toxicolo-y FifthEdition.1996. New York: McGraw-fbll, pages 187-198. Page 8 Table I Half-LifeSummary Data InDays For Those RetireesWith Three CollectionPeriods Whose Log LinearModels Had R 2 > 0.6 PFOS R- > 0.6 R 2 > 0.8 N Mean -Median 18 303 270 16 303 259 Range 95% Cl of Mean 139-640 139-640 228-378 217-388 PFOA R 2 > 0.6 20 389 344 R 2 > 0.8 13 395 324 109-1308 109-1308 269-509 204-585 Page 9